Rabaptin-5alpha/rabaptin-4 serves as a linker between rab4 and gamma(1)-adaptin in membrane recycling from endosomes

EMBO J. 2003 Jun 2;22(11):2645-57. doi: 10.1093/emboj/cdg257.

Abstract

Rab4 regulates recycling from early endosomes. We investigated the role of the rab4 effector rabaptin-5alpha and its putative partner gamma(1)-adaptin in membrane recycling. We found that rabaptin-5alpha forms a ternary complex with the gamma(1)-sigma(1) subcomplex of AP-1, via a direct interaction with the gamma(1)-subunit. The binding site for gamma(1)-adaptin is in the hinge region of rabaptin-5alpha, which is distinct from rab4- and rab5-binding domains. Endogenous or ectopically expressed gamma(1)- adaptin localized to both the trans-Golgi network and endosomes. Co-expressed rabaptin-5alpha and gamma(1)-adaptin, however, co-localized in a rab4-dependent manner on recycling endosomes. Transfection of rabaptin-5alpha caused enlarged endosomes and delayed recycling of transferrin. RNAi of rab4 had an opposing effect on transferrin recycling. Collectively, our data show that rab4-GTP acts as a scaffold for a rabaptin-5alpha- gamma(1)-adaptin complex on recycling endosomes and that interactions between rab4, rabaptin-5alpha and gamma(1)-adaptin regulate membrane recycling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Protein Complex gamma Subunits / chemistry
  • Adaptor Protein Complex gamma Subunits / metabolism*
  • Animals
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Membrane / metabolism
  • Endosomes / metabolism
  • HeLa Cells
  • Humans
  • Macromolecular Substances
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Mice
  • Protein Binding
  • RNA Interference
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Transcription Factor AP-1 / chemistry
  • Transcription Factor AP-1 / metabolism
  • Vesicular Transport Proteins*
  • rab4 GTP-Binding Proteins / chemistry
  • rab4 GTP-Binding Proteins / genetics
  • rab4 GTP-Binding Proteins / metabolism*

Substances

  • Adaptor Protein Complex gamma Subunits
  • Carrier Proteins
  • Macromolecular Substances
  • Membrane Proteins
  • RABEP1 protein, human
  • Rabep1 protein, mouse
  • Recombinant Fusion Proteins
  • Transcription Factor AP-1
  • Vesicular Transport Proteins
  • rab4 GTP-Binding Proteins